Abstract Brazil has a huge number of cases and deaths due to coronavirus disease 2019 (COVID-19); however, few studies have dealt with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among familial contacts in Brazil. Here, we report our findings on transmission in a family-based study in Bauru, São Paulo, Brazil. The study, conducted from July to November 2020, comprised 974 individuals with 233 index patients and 741 familial contacts. Familial contacts were evaluated using the rapid COVID-19 Ag ECO and reverse transcription-polymerase chain reaction (RT-PCR) tests immediately after the index patient diagnosis. The antigen-based rapid test was validated in 121 individuals using RT-PCR as the gold standard. Additionally, 30 days later, familial contacts were evaluated for IgM and IgG antibodies against SARS-CoV-2. We found 333 cases of COVID-19 among familial contacts (44.9%). A positive correlation was observed between the time elapsed from the onset of symptoms until the index patient’s COVID-19 testing and the number of family contacts infected by SARS-CoV-2. Early SARS-CoV-2 testing and familial contact evaluation are relevant strategies to contain transmission.

Resumo O Brasil apresenta um alto número de casos e óbitos por coronavírus (COVID-19), apesar disso, poucos estudos tratavam da infecção pelo coronavirus-2 causador de síndrome respiratória aguda grave (SARS-CoV-2) entre contatos familiares no Brasil. Relatamos aqui nossos achados sobre a transmissão de SARS-CoV-2 em um estudo de base familiar de Bauru, no estado de São Paulo, Brasil. O estudo foi realizado de julho a novembro de 2020 e compreendeu 974 indivíduos, sendo 233 pacientes índice e 741 contatos familiares. Os contatos familiares foram avaliados por meio do teste rápido COVID-19 Ag ECO Test e RT-PCR imediatamente após o diagnóstico do paciente índice. O uso do teste rápido baseado em antígeno foi validado em 121 indivíduos utilizando RT-PCR como padrão ouro. Adicionalmente, 30 dias após a avaliação inicial, os contatos familiares foram avaliados quanto à presença de anticorpos IgM e IgG contra SARS-CoV-2. Encontramos 333 casos de COVID-19 entre contatos familiares (44,9%). Observamos uma correlação positiva entre o tempo decorrido entre o início dos sintomas e o teste para COVID-19 do paciente índice e o número de contatos familiares infectados por SARS-CoV-2. A testagem precoce da infecção por SARS-CoV-2 e a avaliação de contatos familiares são estratégias relevantes para conter a transmissão.

Abstract Brazil has a huge number of cases and deaths due to coronavirus disease 2019 (COVID-19); however, few studies have dealt with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among familial contacts in Brazil. Here, we report our findings on transmission in a family-based study in Bauru, São Paulo, Brazil. The study, conducted from July to November 2020, comprised 974 individuals with 233 index patients and 741 familial contacts. Familial contacts were evaluated using the rapid COVID-19 Ag ECO and reverse transcription-polymerase chain reaction (RT-PCR) tests immediately after the index patient diagnosis. The antigen-based rapid test was validated in 121 individuals using RT-PCR as the gold standard. Additionally, 30 days later, familial contacts were evaluated for IgM and IgG antibodies against SARS-CoV-2. We found 333 cases of COVID-19 among familial contacts (44.9%). A positive correlation was observed between the time elapsed from the onset of symptoms until the index patient’s COVID-19 testing and the number of family contacts infected by SARS-CoV-2. Early SARS-CoV-2 testing and familial contact evaluation are relevant strategies to contain transmission.

Resumo O Brasil apresenta um alto número de casos e óbitos por coronavírus (COVID-19), apesar disso, poucos estudos tratavam da infecção pelo coronavirus-2 causador de síndrome respiratória aguda grave (SARS-CoV-2) entre contatos familiares no Brasil. Relatamos aqui nossos achados sobre a transmissão de SARS-CoV-2 em um estudo de base familiar de Bauru, no estado de São Paulo, Brasil. O estudo foi realizado de julho a novembro de 2020 e compreendeu 974 indivíduos, sendo 233 pacientes índice e 741 contatos familiares. Os contatos familiares foram avaliados por meio do teste rápido COVID-19 Ag ECO Test e RT-PCR imediatamente após o diagnóstico do paciente índice. O uso do teste rápido baseado em antígeno foi validado em 121 indivíduos utilizando RT-PCR como padrão ouro. Adicionalmente, 30 dias após a avaliação inicial, os contatos familiares foram avaliados quanto à presença de anticorpos IgM e IgG contra SARS-CoV-2. Encontramos 333 casos de COVID-19 entre contatos familiares (44,9%). Observamos uma correlação positiva entre o tempo decorrido entre o início dos sintomas e o teste para COVID-19 do paciente índice e o número de contatos familiares infectados por SARS-CoV-2. A testagem precoce da infecção por SARS-CoV-2 e a avaliação de contatos familiares são estratégias relevantes para conter a transmissão.

BACKGROUND Leprosy is a chronic infectious disease caused by Mycobacterium leprae, and compromises the skin and peripheral nerves. This disease has been classified as multibacillary (MB) or paucibacillary (PB) depending on the host immune response. Genetic epidemiology studies in leprosy have shown the influence of human genetic components on the disease outcomes. OBJECTIVES We conducted an association study for IL2RA and TGFB1 genes with clinical forms of leprosy based on two case-control samples. These genes encode important molecules for the immunosuppressive activity of Treg cells and present differential expressions according to the clinical forms of leprosy. Furthermore, IL2RA is a positional candidate gene because it is located near the 10p13 chromosome region, presenting a linkage peak for PB leprosy. METHODS A total of 885 leprosy cases were included in the study; 406 cases from Rondonópolis County (start population), a hyperendemic region for leprosy in Brazil, and 479 cases from São Paulo state (replication population), which has lower epidemiological indexes for the disease. We tested 11 polymorphisms in the IL2RA gene and the missense variant rs1800470 in the TGFB1 gene. FINDINGS The AA genotype of rs2386841 in IL2RA was associated with the PB form in the start population. The AA genotype of rs1800470 in TGFB1 was associated with the MB form in the start population, and this association was confirmed for the replication population. MAIN CONCLUSIONS We demonstrated, for the first time, an association data with the PB form for a gene located on chromosome 10. In addition, we reported the association of TGFB1 gene with the MB form. Our results place these genes as candidates for validation and replication studies in leprosy polarisation.

Abstract Leprosy, whose etiological agent is Mycobacterium leprae, is a chronic infectious disease that mainly affects the skin and peripheral nervous system. The diagnosis of leprosy is based on clinical evaluation, whereas histopathological analysis and bacilloscopy are complementary diagnostic tools. Quantitative PCR (qPCR), a current useful tool for diagnosis of infectious diseases, has been used to detect several pathogens including Mycobacterium leprae. The validation of this technique in a robust set of samples comprising the different clinical forms of leprosy is still necessary. Thus, in this study samples from 126 skin biopsies (collected from patients on all clinical forms and reactional states of leprosy) and 25 slit skin smear of leprosy patients were comparatively analyzed by qPCR (performed with primers for the RLEP region of M. leprae DNA) and routine bacilloscopy performed in histological sections or in slit skin smear. Considering clinical diagnostic as the gold standard, 84.9% of the leprosy patients were qPCR positive in skin biopsies, resulting in 84.92% sensitivity, with 84.92 and 61.22% positive (PPV) and negative (NPV) predictive values, respectively. Concerning bacilloscopy of histological sections (BI/H), the sensitivity was 80.15% and the PPV and NPV were 80.15 and 44.44%, respectively. The concordance between qPCR and BI/H was 87.30%. Regarding the slit skin smear, 84% of the samples tested positive in the qPCR. Additionally, qPCR showed 100% specificity, since all samples from different mycobacteria, from healthy individuals, and from other granulomatous diseases presented negative results. In conclusion, the qPCR technique for detection of M. leprae using RLEP primers proved to be specific and sensitive, and qPCR can be used as a complementary test to diagnose leprosy irrespective of the clinical form of disease.

FUNDAMENTOS: Na hanseníase dimorfa é comum a ocorrência de reações tipo 1 antes, durante ou depois da poliquimioterapia (PQT). Trabalhos recentes sugerem que a reação tipo 1 seria um desequilíbrio imunológico entre citocinas pró-inflamatórias e antiinflamatórias. OBJETIVOS: Compreender melhor a fisiopatologia das reações tipo 1. MÉTODOS: Estudaram-se biópsias cutâneas de 10 indivíduos com hanseníase dimorfa-tuberculóide reacional não tratada (DTR) e 10 dimorfos em reação reversa após o início da PQT (DRR), comparando-se os parâmetros morfológicos e imunológicos por meio de colorações HE e Faraco-Fite, e técnicas imuno-histoquímicas (CD4, CD8, CD20, CD79a, CD57, iNOS, IL-10, LAM e BCG). RESULTADOS: Houve, nos DRR, mais macrófagos multivacuolados, maior marcação nos macrófagos para a enzima óxido nítrico sintase induzível (iNOS) e menos linfócitos T CD8+ (p<0,05). Afora a presença de bacilos típicos nos DTR e sua ausência nos DRR, não houve diferenças na baciloscopia ou na marcação para antígenos micobacterianos (LAM e BCG) entre os grupos. O número de células IL-10+ foi similar nos dois grupos, porém houve correlação negativa entre essa citocina e a proporção CD4/CD8 apenas nos pacientes DRR (p<0,05). Houve tendência à redução do infiltrado específico e ao maior número de células NK nos DRR. CONCLUSÃO: Na presença de muitos bacilos viáveis em um paciente sem imunidade celular plena, haveria tendência à piora imunológica (downgrading). A PQT, ao reduzir a carga bacilar, melhoraria a imunidade celular (upgrading), com posterior desvio da imunidade adquirida para a inespecífica (resposta Th3), evoluindo para a cura.

BACKGROUND: Type 1 reactions are common in borderline leprosy, and can occur before, during or after multidrugtherapy (MDT). Recent papers suggest that these reactions could be a result of an imbalance between proinflammatory and anti-inflammatory citokines. OBJECTIVE: To understand better the physiopathology of type 1 reactions. METHODS: We studied skin biopsies from 10 non-treated patients with reactional borderline tuberculoid leprosy (BTR) and 10 from borderline leprosy with reversal reactions after the beginning of MDT (BRR), to compare morphological and immunological parameters by routine staining (H-E and Faraco-Fite) and immunohistochemical technics (CD4, CD8, CD20, CD79a, CD57, iNOS, IL-10, LAM and BCG). RESULTS: We found, in BRR group, stronger staining for iNOS into macrofages, fewer CD8+ T cells and more multivacuolated macrofages than BTR group (p<0,05). Despite the presence of viable bacilli in BTR and its absence in BRR, there weren't differences in baciloscopy and staining for mycobacterial antigens (LAM and BCG) between the groups. The number of IL-10+ cells was similar in both groups, but there was a negative correlation between this cytokine and the CD4:CD8 ratio only in BRR group (p<0,05). It was seen a tendency for a decreased specific infiltrate and increased number of NK cells in BRR group. CONCLUSIONS: The presence of many viable bacilli in a patient with partial cellular immunity could worse the immunological status (downgrading). Once started MDT, the reduction bacilli charge would improve cellular immunity (upgrading), with latter shift to innate immunity (Th3 response), evolving to cure.